Currently, the only approved therapy for acute ischemic stroke is tissue plasminogen activator (tPA), initiated within 3 hours of stroke onset. New patient selection criteria are emerging that may improve the effectiveness and safety of thrombolysis. For example, evidence of extensive early ischemia on CT may predict a poor outcome regardless of whether tPA is administered. New imaging techniques, such as diffusion MRI, perfusion MRI, and MR angiography, may be able to identify salvageable tissue and distinguish it from irreversibly damaged tissue. Such findings may allow the 3-hour window for tPA therapy to be extended in certain patients. Other approaches to ischemic stroke therapy that are being studied include intra-arterial thrombolysis, new thrombolytic agents, platelet aggregation inhibitors, endovascular interventional techniques (alone and in combination with pharmacologic thrombolysis), and neuroprotective therapy with various agents to ameliorate the consequences of ischemia in brain tissue.